Cushing's SyndromePhase 3SEISMICNCT00569582
A Study of the Efficacy and Safety of CORLUX in the Treatment of Endogenous Cushing's Syndrome
A Phase 3 study testing mifepristone in people with Cushing's Syndrome, run by Corcept Therapeutics at 17 sites in United States.
Trial summary
Patients will receive Corlux (mifepristone) daily for up to 24 weeks. Assessments of the signs and symptoms of Cushing's syndrome will be obtained. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cushing's Syndrome
- What is being tested?
- mifepristone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 17 sitesUnited States
- Study dates
- Dec 2007to Jan 2011
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Individuals eligible for enrollment into this study are adult male and non-pregnant female adult patients who:
- Are at least 18 years of age
- Have a confirmed diagnosis of endogenous hypercortisolemia caused by ACTH dependent or ACTH independent etiologies, including
- Cushing's Disease (that has recurred after primary pituitary surgery, or has failed pituitary surgery, or has been treated with radiation therapy to the pituitary, or is not treatable with surgery, or exists in patients who are not candidates for surgery, and is confirmed by documentation of ACTH immuno-reactivity on a pathological evaluation of pituitary tissue from a previous surgical specimen or IPSS with a central-to-peripheral gradient (ratio) of >2 before or >3 after CRH administration).
- Ectopic ACTH
- Ectopic CRF secretion
Show all 11Show fewer
- Adrenal adenoma
- Adrenal carcinoma
- Adrenal autonomy
- Require medical treatment of hypercortisolemia
- Have diabetes mellitus type 2 or glucose intolerance AND/OR have hypertension *Note: To be eligible for inclusion subjects must have documented evidence of persistent endogenous hypercortisolemia
Who cannot join
- Individuals not eligible to be enrolled into the study are those who:
- Have de novo Cushing's disease and are surgical candidates for pituitary surgery.
- Have an acute or unstable medical problem, which could be aggravated by mifepristone treatment.
- Taking medications within 14 days of the baseline visit (Day 1) that a) have a large first pass metabolism largely mediated by CYP3A4 and a narrow therapeutic margin and/or b) are strong CYP3A4 inhibitors.
- Female patients of reproductive potential, who are pregnant or who are unable or unwilling to use medically acceptable, non-hormonal methods of contraception during the study.
- Have received investigational treatment (drug, biological agent or device) within 30 days of Screening
Show all 12Show fewer
- Have a history of an allergic reaction or intolerance to CORLUX (mifepristone)
- Have a non-endogenous source of hypercortisolemia such as factious hypercortisolemia (exogenous source of glucocorticoid, iatrogenic Cushing's syndrome), factious or therapeutic use of ACTH
- Have Pseudo-Cushing's syndrome.
- Receive PPARgamma agonist drugs (e.g. pioglitazone, rosiglitazone) within 4 months of Baseline (Day 1).
- Postmenopausal women with an intact uterus who have experienced unexplained vaginal bleeding within 12 months of Screening are excluded.
- Have renal failure as defined by a serum creatinine of ≥2.2 mg/dL.
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
United States17 sites
University of New Mexico HSC
Albuquerque, New Mexico, 87131
University of Michigan Medical Center
Ann Arbor, Michigan, 48109
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215
University of Alabama at Birmingham School of Medicine
Birmingham, Alabama, 35294
Massachusetts General Hospital
Boston, Massachusetts, 02114
Northwestern University Feinberg Medical; Division of Endocrinology, Metabolism & Molecular Medicine
Chicago, Illinois, 60611
The University of Chicago
Chicago, Illinois, 60637
Cleveland Clinic Foundation; Dept of Endocrinology, Diabetes & Metabolism
Cleveland, Ohio, 44195
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
AMCR Institute Inc.
Escondido, California, 92026
The Center for Diabetes and Endocrine Care
Hollywood, Florida, 33021
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Endocrinology Center at North Hills, Froedtert and Medical College of Wisconsin
Menomonee Falls, Wisconsin, 53051
Oklahoma University Health Science Center
Oklahoma City, Oklahoma, 73104
Oregon Health Sciences University
Portland, Oregon, 97239
Diabetes and Glandular Disease Clinic
San Antonio, Texas, 78229
Stanford University Medical Center
Stanford, California, 94305-5826
About this study
Official title: An Open-label Study of the Efficacy and Safety of CORLUX (Mifepristone) in the Treatment of the Signs and Symptoms of Endogenous Cushing's Syndrome
Patients will receive Corlux (mifepristone) daily for up to 24 weeks. Assessments of the signs and symptoms of Cushing's syndrome will be obtained.
Read the detailed description
Cushing's syndrome is a relatively rare disorder caused by prolonged exposure to high levels of the glucocorticoid hormone cortisol. Cushing's syndrome may result from elevated endogenous or exogenous sources of cortisol. Endogenous Cushing's syndrome resulting from cortisol overproduction by the adrenal glands is the subject of this protocol. Patients with exogenous Cushing's syndrome, which develops as a side effect of chronic administration of high doses of glucocorticoids, are not eligible for enrollment in this study.
This will evaluate the safety and efficacy of mifepristone for treatment of the signs and symptoms of hypercortisolemia in patients with endogenous Cushing's syndrome from ACTH-dependent or adrenal disorders.
The study will enroll subjects for whom the investigator has determined that medical treatment of endogenous hypercortisolemia is needed. Medical treatment may be intended to treat the effects of persistent or recurrent hypercortisolemia after surgery and/or radiation for Cushing's syndrome, to bridge the period of time for radiation to become effective, or when surgery is not feasible.
- Conditions
- Cushing's Syndrome
- Being tested
- mifepristone
- Keywords
- Cushing's Disease, Cushing's Syndrome, Cushings, Pituitary, ACTH, Adrenocorticotropic hormone, Ectopic, Adrenal adenoma, Adrenal carcinoma, Adrenal autonomy, Cortisol, Hypercortisolemia, Cushingoid, Moon facies, Dorsocervical fat, Plethora, Hirsutism, Violaceous striae, Hormone, Contraceptive
- Medical subject headings
- Cushing Syndrome, Pituitary ACTH Hypersecretion, Pituitary Diseases, Choristoma, ACTH Syndrome, Ectopic, Adrenal Cortex Neoplasms, Hirsutism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mifepristoneDrug
Also called CORLUX
Patients take mifepristone by mouth once a day. The dose is increased during scheduled timepoints during the study or until symptoms improve or the highest dosage allowed is reached. Dose escalation will be based upon weight. During clinic visits, blood pressure, glucose tolerance and blood chemistries are measured and EKG and urinalysis will be performed.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: mifepristone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement in Diabetes and/or Glucose Intolerance.
Responder is defined as subject with a decrease greater than or equal to 25% in area under the curve for glucose on 2-hour oral glucose test from baseline to week 24 or last visit, for Cushing's patients with type-2 diabetes mellitus/impaired glucose tolerance.
Measured: Baseline to Week 24
Decrease in Diastolic Blood Pressure.
Responder is defined as subject with a decrease greater than or equal to 5mm Hg in diastolic blood pressure from baseline to week 24 or last visit.
Measured: Baseline to Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2007 (estimated)
- Study startDec 2007
- Primary completionJan 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Cushing's SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Corcept Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Coleman Gross, Study director, Corcept Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00569582
- Sponsor's protocol ID
- C-1073-400
- Acronym
- SEISMIC
- Status last verified
- Aug 2013
- First submitted
- 5 Dec 2007
- Last updated
- 22 Aug 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Sartor O, Cutler GB Jr. Mifepristone: treatment of Cushing's syndrome. Clin Obstet Gynecol. 1996 Jun;39(2):506-10. doi: 10.1097/00003081-199606000-00024.
PubMed 8734015Johanssen S, Allolio B. Mifepristone (RU 486) in Cushing's syndrome. Eur J Endocrinol. 2007 Nov;157(5):561-9. doi: 10.1530/EJE-07-0458.
PubMed 17984235Morris D, Grossman A. The medical management of Cushing's syndrome. Ann N Y Acad Sci. 2002 Sep;970:119-33. doi: 10.1111/j.1749-6632.2002.tb04418.x.
PubMed 12381547Chu JW, Matthias DF, Belanoff J, Schatzberg A, Hoffman AR, Feldman D. Successful long-term treatment of refractory Cushing's disease with high-dose mifepristone (RU 486). J Clin Endocrinol Metab. 2001 Aug;86(8):3568-73. doi: 10.1210/jcem.86.8.7740.
PubMed 11502780Agarwai MK. The antiglucocorticoid action of mifepristone. Pharmacol Ther. 1996;70(3):183-213. doi: 10.1016/0163-7258(96)00016-2.
PubMed 8888066Miller JW, Crapo L. The medical treatment of Cushing's syndrome. Endocr Rev. 1993 Aug;14(4):443-58. doi: 10.1210/edrv-14-4-443. No abstract available.
PubMed 7693447Nieman LK, Chrousos GP, Kellner C, Spitz IM, Nisula BC, Cutler GB, Merriam GR, Bardin CW, Loriaux DL. Successful treatment of Cushing's syndrome with the glucocorticoid antagonist RU 486. J Clin Endocrinol Metab. 1985 Sep;61(3):536-40. doi: 10.1210/jcem-61-3-536.
PubMed 2991327Fleseriu M, Biller BM, Findling JW, Molitch ME, Schteingart DE, Gross C; SEISMIC Study Investigators. Mifepristone, a glucocorticoid receptor antagonist, produces clinical and metabolic benefits in patients with Cushing's syndrome. J Clin Endocrinol Metab. 2012 Jun;97(6):2039-49. doi: 10.1210/jc.2011-3350. Epub 2012 Mar 30.
PubMed 22466348Fein HG, Vaughan TB 3rd, Kushner H, Cram D, Nguyen D. Sustained weight loss in patients treated with mifepristone for Cushing's syndrome: a follow-up analysis of the SEISMIC study and long-term extension. BMC Endocr Disord. 2015 Oct 27;15:63. doi: 10.1186/s12902-015-0059-5.
PubMed 26507877Fleseriu M, Findling JW, Koch CA, Schlaffer SM, Buchfelder M, Gross C. Changes in plasma ACTH levels and corticotroph tumor size in patients with Cushing's disease during long-term treatment with the glucocorticoid receptor antagonist mifepristone. J Clin Endocrinol Metab. 2014 Oct;99(10):3718-27. doi: 10.1210/jc.2014-1843. Epub 2014 Jul 11.
PubMed 25013998Wallia A, Colleran K, Purnell JQ, Gross C, Molitch ME. Improvement in insulin sensitivity during mifepristone treatment of Cushing syndrome: early and late effects. Diabetes Care. 2013 Sep;36(9):e147-8. doi: 10.2337/dc13-0246. No abstract available.
PubMed 23970725
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Study of the Efficacy and Safety of CORLUX (Mifepristone) in the Treatment of the Signs and Symptoms of Endogenous Cushing's Syndrome
- ClinicalTrials.gov ID
- NCT00569582
- Acronym / sponsor ID
- SEISMIC / C-1073-400
- Conditions
- Cushing's Syndrome
- Keywords
- Cushing's Disease, Cushing's Syndrome, Cushings, Pituitary, ACTH, Adrenocorticotropic hormone, Ectopic, Adrenal adenoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Corcept TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Dec 2007
- Primary completion
- Jan 2011 (actual)
- First posted
- 7 Dec 2007 (estimated)
- Results
- Posted 28 May 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients will receive Corlux (mifepristone) daily for up to 24 weeks. Assessments of the signs and symptoms of Cushing's syndrome will be obtained.
Detailed description
Cushing's syndrome is a relatively rare disorder caused by prolonged exposure to high levels of the glucocorticoid hormone cortisol. Cushing's syndrome may result from elevated endogenous or exogenous sources of cortisol. Endogenous Cushing's syndrome resulting from cortisol overproduction by the adrenal glands is the subject of this protocol. Patients with exogenous Cushing's syndrome, which develops as a side effect of chronic administration of high doses of glucocorticoids, are not eligible for enrollment in this study.
This will evaluate the safety and efficacy of mifepristone for treatment of the signs and symptoms of hypercortisolemia in patients with endogenous Cushing's syndrome from ACTH-dependent or adrenal disorders.
The study will enroll subjects for whom the investigator has determined that medical treatment of endogenous hypercortisolemia is needed. Medical treatment may be intended to treat the effects of persistent or recurrent hypercortisolemia after surgery and/or radiation for Cushing's syndrome, to bridge the period of time for radiation to become effective, or when surgery is not feasible.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: mifepristone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Individuals eligible for enrollment into this study are adult male and non-pregnant female adult patients who:
- Are at least 18 years of age
- Have a confirmed diagnosis of endogenous hypercortisolemia caused by ACTH dependent or ACTH independent etiologies, including
- Require medical treatment of hypercortisolemia
- Have diabetes mellitus type 2 or glucose intolerance AND/OR have hypertension *Note: To be eligible for inclusion subjects must have documented evidence of persistent endogenous hypercortisolemia
Key exclusion criteria (12 listed)
- Have de novo Cushing's disease and are surgical candidates for pituitary surgery.
- Have an acute or unstable medical problem, which could be aggravated by mifepristone treatment.
- Taking medications within 14 days of the baseline visit (Day 1) that a) have a large first pass metabolism largely mediated by CYP3A4 and a narrow therapeutic margin and/or b) are strong CYP3A4 inhibitors.
- Female patients of reproductive potential, who are pregnant or who are unable or unwilling to use medically acceptable, non-hormonal methods of contraception during the study.
- Have received investigational treatment (drug, biological agent or device) within 30 days of Screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| mifepristoneAlso: CORLUXPatients take mifepristone by mouth once a day. The dose is increased during scheduled timepoints during the study or until symptoms improve or the highest dosage allowed is reached. Dose escalation will be based upon weight. During clinic visits, blood pressure, glucose tolerance and blood chemistries are measured and EKG and urinalysis will be performed. | Drug | 1 |
Primary outcome
Improvement in Diabetes and/or Glucose Intolerance.
Time frame: Baseline to Week 24
Responder is defined as subject with a decrease greater than or equal to 25% in area under the curve for glucose on 2-hour oral glucose test from baseline to week 24 or last visit, for Cushing's patients with type-2 diabetes mellitus/impaired glucose tolerance.
Decrease in Diastolic Blood Pressure.
Time frame: Baseline to Week 24
Responder is defined as subject with a decrease greater than or equal to 5mm Hg in diastolic blood pressure from baseline to week 24 or last visit.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 8734015Sartor O, Cutler GB Jr. Mifepristone: treatment of Cushing's syndrome. Clin Obstet Gynecol. 1996 Jun;39(2):506-10. doi: 10.1097/00003081-199606000-00024.
- Background: PubMed 17984235Johanssen S, Allolio B. Mifepristone (RU 486) in Cushing's syndrome. Eur J Endocrinol. 2007 Nov;157(5):561-9. doi: 10.1530/EJE-07-0458.
- Background: PubMed 12381547Morris D, Grossman A. The medical management of Cushing's syndrome. Ann N Y Acad Sci. 2002 Sep;970:119-33. doi: 10.1111/j.1749-6632.2002.tb04418.x.
- Background: PubMed 11502780Chu JW, Matthias DF, Belanoff J, Schatzberg A, Hoffman AR, Feldman D. Successful long-term treatment of refractory Cushing's disease with high-dose mifepristone (RU 486). J Clin Endocrinol Metab. 2001 Aug;86(8):3568-73. doi: 10.1210/jcem.86.8.7740.
- Background: PubMed 8888066Agarwai MK. The antiglucocorticoid action of mifepristone. Pharmacol Ther. 1996;70(3):183-213. doi: 10.1016/0163-7258(96)00016-2.
- Background: PubMed 7693447Miller JW, Crapo L. The medical treatment of Cushing's syndrome. Endocr Rev. 1993 Aug;14(4):443-58. doi: 10.1210/edrv-14-4-443. No abstract available.
- Background: PubMed 2991327Nieman LK, Chrousos GP, Kellner C, Spitz IM, Nisula BC, Cutler GB, Merriam GR, Bardin CW, Loriaux DL. Successful treatment of Cushing's syndrome with the glucocorticoid antagonist RU 486. J Clin Endocrinol Metab. 1985 Sep;61(3):536-40. doi: 10.1210/jcem-61-3-536.
- Results publication: PubMed 22466348Fleseriu M, Biller BM, Findling JW, Molitch ME, Schteingart DE, Gross C; SEISMIC Study Investigators. Mifepristone, a glucocorticoid receptor antagonist, produces clinical and metabolic benefits in patients with Cushing's syndrome. J Clin Endocrinol Metab. 2012 Jun;97(6):2039-49. doi: 10.1210/jc.2011-3350. Epub 2012 Mar 30.
- Derived from this study: PubMed 26507877Fein HG, Vaughan TB 3rd, Kushner H, Cram D, Nguyen D. Sustained weight loss in patients treated with mifepristone for Cushing's syndrome: a follow-up analysis of the SEISMIC study and long-term extension. BMC Endocr Disord. 2015 Oct 27;15:63. doi: 10.1186/s12902-015-0059-5.
- Derived from this study: PubMed 25013998Fleseriu M, Findling JW, Koch CA, Schlaffer SM, Buchfelder M, Gross C. Changes in plasma ACTH levels and corticotroph tumor size in patients with Cushing's disease during long-term treatment with the glucocorticoid receptor antagonist mifepristone. J Clin Endocrinol Metab. 2014 Oct;99(10):3718-27. doi: 10.1210/jc.2014-1843. Epub 2014 Jul 11.
- Derived from this study: PubMed 23970725Wallia A, Colleran K, Purnell JQ, Gross C, Molitch ME. Improvement in insulin sensitivity during mifepristone treatment of Cushing syndrome: early and late effects. Diabetes Care. 2013 Sep;36(9):e147-8. doi: 10.2337/dc13-0246. No abstract available.
- Corporate WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Coleman Gross study director
Corcept Therapeutics
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing mifepristone in people with Cushing's Syndrome, run by Corcept Therapeutics at 17 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 May 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement in Diabetes and/or Glucose Intolerance. (time frame: Baseline to Week 24). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00569582, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2013.